ADRESA
Put doktora Goldmana 4
Sremska Kamenica
Srbija
PIŠITE NAM
senologija@gmail.com
SAŽETAK
Sanja Jelaˇca 1
, Ivan Jovanovic 2
, Dijana Bovan 1
, Marina Z. Jovanovic 3
, Milena M. Jurisevic 4
,
Duško Dunderovi´c ¯
5
, Zora Dajic-Stevanovic 6
, Nebojsa Arsenijevic 2
, Sanja Mijatovi´c 1,*
and Danijela Maksimovi´c-Ivani´c 1,*
1 Department of Immunology, Institute for Biological Research “Siniša Stankovi´c”—National Institute of the
Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia;
sanja.jelaca@ibiss.bg.ac.rs (S.J.); dijana.draca@ibiss.bg.ac.rs (D.B.)
2 Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac,
Svetozara Markovi´ca 69, 34000 Kragujevac, Serbia; ivanjovanovic77@gmail.com (I.J.);
nebojsa_arsenijevic@yahoo.com (N.A.)
3 Department of Otorhinolaryngology, Faculty of Medical Sciences, University of Kragujevac,
34000 Kragujevac, Serbia; marina_jovanovic@rocketmail.com
4 Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia;
milena.jurisevic13@gmail.com
5
Institute of Pathology, School of Medicine, University of Belgrade, Dr Suboti´ca 8, 11000 Belgrade, Serbia;
dusko.dundjerovic@med.bg.ac.rs
6 Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11080 Belgrade, Serbia; dajic@agrif.bg.ac.rs
* Correspondence: sanjamama@ibiss.bg.ac.rs (S.M.); nelamax@ibiss.bg.ac.rs (D.M.-I.);
Tel.: +381-11-2078452 (S.M. & D.M.-I.)
Abstract: Ethnomedicinal records have long mentioned the historical usage of Alchemilla vulgaris L. in
folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal
knowledge regarding female illnesses, the aim of this research was to evaluate the impact of ethanolic
extract of A. vulgaris on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect
on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells
induced by treatment with A. vulgaris extract was strong inhibition of cell proliferation accompanied
by caspase-dependent apoptosis and autophagic cell death. Observed changes in 4T1 cell culture
after treatment were well orchestrated and led to a reduction in metastatic potential through weakened adhesion, invasion, migration, and colony-forming abilities in vitro. Enhanced intracellular
production of reactive oxygen and nitrogen species promoted by the treatment might interfere with
all the observed effects. Apart from the direct effect on tumor cells, the A. vulgaris extract significantly
reduced tumor growth in the solid orthotropic mammary carcinoma model through restitution of
efficient local and systemic immune response reflected in enhanced antigen-presenting potential of
dendritic cells (DCs) as well as the extent and activity of effector T cells.
Keywords: Alchemilla vulgaris L.; breast cancer; apoptosis; tumor microenvironment; immune
response